Office-based cardiovascular risk prediction continues to challenge practitioners in primary and secondary risk stratification settings. In patients with established peripheral arterial disease (PAD), the risk of cardiovascular events (i.e. death or morbidity due to coronary heart disease and/or cerebrovascular disease) is high, yet traditional risk factors and the ankle-brachial index (ABI) do not provide a complete secondary risk prediction. In this population, office-based cardiovascular risk stratification may be improved by surrogate markers of the systemic atherosclerotic burden, as well as markers of systemic inflammation. This review will evaluate the utility of the ABI, clinical stage of disease, and the emerging role of C-reactive protein (CRP) and other inflammatory markers in secondary risk prediction in PAD. Defining which patients are in the highest category of risk may direct health care providers to emphasize secondary preventive measures, and facilitate patient adherence to recommended medical therapies and smoking cessation.